A Study of TAK-330 to Reverse the Effects of Factor Xa Inhibitors For Adults Needing Urgent Surgery

Launched by TAKEDA · Dec 13, 2021

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called TAK-330, which aims to reverse the effects of certain blood thinners known as Factor Xa inhibitors (like rivaroxaban, apixaban, and edoxaban). These medications can increase the risk of bleeding, especially during urgent surgeries. The trial will compare TAK-330 to a standard treatment called four-factor prothrombin complex concentrate (4F-PCC) to see which is more effective at preventing bleeding during surgery.

To be eligible for the trial, participants must be at least 18 years old, currently using a Factor Xa inhibitor, and in need of urgent surgery within 15 hours of their last dose of the medication. Participants will be hospitalized for the surgery and will receive either TAK-330 or the standard treatment. After the surgery, they will have a follow-up call 30 days later to check on their recovery. This study is currently recruiting participants and aims to help improve safety for patients needing urgent surgical procedures while on blood thinners.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Participant or legally authorized representative willing to sign e-consent/written informed consent form.
• • Participants at least 18 years of age at enrollment.
• • Participant currently on treatment with oral Factor Xa inhibitor (rivaroxaban, apixaban, edoxaban).
• • In the opinion of the surgeon, the participant requires an urgent surgery/procedure that is associated with high-risk of intraoperative bleeding within 15 hours from the last dose of Factor Xa inhibitor and requires a reversal agent for suspected direct oral Factor Xa inhibitor-related coagulopathy. For participants who are beyond the 15-hour window, eligibility requires proof of elevated plasma anti-Factor Xa (FXa) levels using either specific direct oral anti-coagulant (DOAC)-calibrated (apixaban, rivaroxaban or edoxaban) anti-FXa levels of greater than (\>) 75 nanograms per milliliter (ng/mL), or heparin calibrated anti-FXa assay levels of \>0.5 international unit per milliliter (IU/mL) at screening.
• • Women of childbearing potential should have a negative pregnancy test documented prior to enrollment.
• Exclusion Criteria:
• • The participant has an expected survival of less than 30 days, even with best available medical and surgical care.
• • Recent history (within 90 days prior to screening) of venous thromboembolism, myocardial infarction (MI), disseminated intravascular coagulation (DIC), ischemic stroke, transient ischemic attack, hospitalization for unstable angina pectoris or severe or critical coronavirus 2 (SARS-CoV-2) infection.
• • Active major bleeding defined as bleeding that requires surgery or transfusion of \>2 units of packed red blood cell (PRBC) or intracranial hemorrhage with the exception of subacute and chronic subdural hemorrhages with a Glasgow Coma Score (GCS) greater than or equal to (\>=) 9.
• • Polytrauma for which reversal of Factor Xa-inhibition alone would not be sufficient to achieve hemostasis.
• • Known prothrombotic disorder including primary antiphospholipid syndrome, antithrombin-3 deficiency, homozygous protein C deficiency, homozygous protein S deficiency, and homozygous factor V Leiden.
• • Known bleeding disorder (example, platelet function disorders, hemophilia, Von Willebrand disease, or coagulation factor deficiency).
• • Platelet count less than (\<) 50,000 per microliter (/mcL).
• • History of heparin-induced thrombocytopenia.
• • Administration of procoagulant drugs (example, non-study prothrombin complex concentrates (PCCs), recombinant Factor VIIa) or blood products (transfusion of whole blood, fresh frozen plasma, cryoglobulins, plasma fractions, or platelets) within 7 days before enrollment. (Note: administration of PRBCs for hemoglobin correction, tranexamic acid or aminocaproic acid are not exclusion criteria).
• • Planned use of procoagulant drugs (example, Vitamin K, non-study PCCs, recombinant Factor VIIa) or blood products (transfusion of whole blood, fresh frozen plasma, cryoglobulins, plasma fractions, or platelets) after enrollment but before the 24±4 hours hemostatic assessment (Key secondary endpoint). Planned administration of tranexamic acid (TXA) or aminocaproic acid after randomization but before the start of IP infusion, should be noted during randomization to properly stratify these participants in the interactive response technology (IRT). Planned administration of TXA or aminocaproic acid after start of IP infusion but before the 24±4 hours hemostatic assessment is prohibited. Administration of any of the above products before the 24±4 hours hemostatic assessment will impact the assessment of hemostasis. Administration of PRBCs for hemoglobin correction, is not an exclusion criterion.
• • Administration of unfractionated heparin within 2 hours before randomization or low molecular weight heparin within 6 hours before randomization.
• • Hypersensitivity to PCC constituents or any excipient of TAK-330.
• • Participants with history of confirmed immunoglobulin A (IgA) deficiency with hypersensitivity reaction and antibodies to IgA.
• • Septic shock as defined by persistent hypotension requiring vasopressors to maintain mean arterial pressure (MAP) \>=65 millimeters of mercury (mmHg) and having blood lactate \>2 millimole (mmol) despite adequate volume resuscitation.
• • Acute or chronic liver failure (hepatic cirrhosis Child-PUGH score C)
• • Renal failure requiring dialysis
• • Any other condition that could, in the opinion of the investigator, put the participant at undue risk of harm if the participant were to participate in the study.
• • Participation in another clinical study involving an investigational product or device within 30 days prior to study enrollment, or planned participation in another clinical study involving an investigational product or device during the course of this study. Participation in an observational study is not an exclusion criterion.
• • The use of PROTHROMPLEX TOTAL as SOC 4F-PCC.
• • Women who are breastfeeding at the time of enrollment.